Abstract

Visualizations of complex biological structures such as viruses are
well-suited to distribution via the electronic medium of the World Wide
Web, complementing the peer-reviewed publication of figures in
scientific papers. Animation and color can be employed to accentuate
particular features of structure, and thus a greater information
content can be imparted than would be possible with printed media.
Structural information that is easily accessible in a standard,
meaningful, and even interactive format can be an effective tool in
teaching and research. We at the Institute for Molecular Virology,
University of Wisconsin-Madison have developed a World Wide Web server (http://www.bocklabs.wisc.edu/Welcome.html) (http://www.virology.wisc.edu/virusworld) * which disseminates structural information in novel formats world-wide to scientists, teachers, students, and the public.

Animations, interactive models, and high resolution color-coded images
of viral particles and proteins are available, many of them
exclusively, from our site. To create comparable visualizations using
generally available resources would prove difficult, to a large extent
because of the complexity of these structures which would require
specialized computing equipment, a great deal of computing expertise,
and datasets that are either not publicly available or that need to be
reconstructed by symmetry operations from the PDB coordinates (which
represent one sixtieth of the complete particle). The previously
rendered images and animations, however, can be readily downloaded and
viewed on personal computers connected to the Web.

We have used animation and false color extensively to present
structural details that may not have been visible without additional
figures, such as orthogonal or radial sections, multiple views, or
stereoscopic images. Coloring the virus particle according to the
protein subunits (Fig. 1a) allows the viewer to determine the
composition of notable structural elements on the particle surface.
Radial depth cueing [1]
(Fig. 1b) is a technique for applying false color that correlates with
the radial distance from the center of the particle. We often use these
coloring techniques in conjunction with animation techniques. Both spin
animation, i.e. rotation of the particle around an axis (Fig. 2a), and
radial depth cueing are effective in enhancing the surface topography
and improving the presentation of peaks, canyons, and pores. The
cropping of frontal (Fig. 2b) or radial (Fig. 2c) sections reveals
internal features.

FIGURE 1: Two types of false color are applied to virus structures. a.) Color
corresponds to the protein subunit. Human rhinovirus 14 (a common cold virus) [6];
VP1 (Viral Protein 1) is colored blue, VP2 green, and VP3 red (VP4 is inside and not
visible). Rendered using srf [7] on a Silicon Graphics workstation. b.) Color is a function
of the distance from the center of the particle, i.e. radial depth cueing [1]. Flock house
virus (an insect virus) [8]. Rendered using Spline [9] and MIDAS-Plus [10] on a Silicon Graphics [11]
workstation.

FIGURE 2: Three types of animation were used to display the virus structures. The core particle of mammalian
reovirus[12], shown with radial depth cueing. a.) Rotation around an axis (spin animation). b.) Cropping in the z-
direction. c.) Radial cropping. Rendered using Iris Explorer [13] on a Silicon Graphics workstation.

We offer yet another useful representation of virus crystal structure
data, one that takes advantage of the capability of the WWW protocol to
“view” atomic coordinate files interactively [2]:
a three-dimensional model of an icosahedral asymmetric unit of the
virus, displayed in the context of the icosahedral framework (Fig. 3).
These interactive models employ the KineMAGE [3]
molecular graphics program as a helper application that needs to be
installed on the user's computer. We also anticipate offering
"navigable" QuickTime [4]
movies of rendered virus structures in the near future, which will
provide even greater flexibility by alleviating the requirement of a
molecular graphics helper program, yet still allowing the real-time
manipulation of these structures in three dimensions.

This type
of electronic publishing has marked advantages over a CD-ROM because it
can be updated instantly. Unlike a CD-ROM, performance is affected by
Internet bandwith limitations, namely the type of connection and
overall Internet traffic. Once the animation or structural file has
been transferred, however, all manipulation becomes local to the user's
machine, and thus these visualizations truly offer real-time
interactivity.

These virus visualizations enhance conventional virology instruction by
offering unique resources to students and teachers. Animated or
interactive visualizations of viruses allow students to interact in new
ways with the course material and can supplement traditional teaching
aids such as textbooks and lectures. With advances like the World Wide
Web protocol and Kinemage, electronic publishing of virus structures
have become decreasingly less platform-dependent and thus the are now
accessible to a much wider audience. In addition to these
visualizations, we provide other course materials on our server, such
as virology tutorials, course notes, syllabi, and journal articles.
This material is most effectively assembled into a coherent whole by
the teachers who are on the 'front lines,' not by us as electronic
publishers. To achieve this end, we have designed a fill-in form
interface that allows instructors without any knowledge of HTML
(HyperText Markup Language) [11]
to create clickable course outlines ("hypersyllabi") which are
maintained on our server. This coupled approach of providing useful
information in unique, multimedia formats and a dynamic environment for
organizing the information will, we believe, enhance distance education
and collaborative teaching.

Acknowledgments

We gratefully acknowledge Jack E. Johnson
and colleagues at the Structural Biology Group at Purdue University for
supplying us with the atomic coordinates that were used to generate
Figure 1b and Timothy S. Baker and colleagues also at Purdue University
for supplying us with the three-dimensional cryo-electron microscopy
dataset that was used to generate Figure 2.

This work was performed at the Institute for Molecular Virology,
University of Wisconsin-Madison, with partial funding provided by the
Lucille P. Markey Charitable Trust. Work in establishing the WWW Server
for Virology was used to fulfill part of the requirements for awarding
the Masters of Science degree in Biochemistry (5-95) to S.M.S. for work
he performed in the laboratory of Prof. Max L. Nibert.